A survey of 48 isolates of the entomopathogenic fungus Metarhizium anisopliae
for production of the anti-cancer indolizidine alkaloid swainsonine revealed that 55% of
the strains of the haploid variety anisopliae produced swainsonine as did 30% of the
strains of the diploid variety majus. There was no evidence of either geographical
restriction of producer strains or of any host preference.
Only two isolates of M anisopliae vaL anisopliae produced high concentrations
of swain so nine in submerged liquid culture and one of these (lMl 147690) was used to
investigate the physiology of swainsonine production in shake flask cultures and 3.5
litre fermentations. Conditions were optimised and the process was scaled up to
production from a 400 litre fermentation that was estimated to have produced over 30g
of swainsonine after 87 hours. A simple and efficient isolation process was developed to
purify swainsonine from the fermentation broth and despite minor technical problems
during the isolation, the final yield of 10.36g was considerably higher than previously
reported from other fermentations of this species. These improvements could be
commercially important should this currently expensive alkaloid progress further
through clinical trials.
Swainsonine was also shown for the first time to be produced by M. anisopfiae
during insect parasitism. Analysis oflepidopteran larvae artificially infected with isolate
IMI 147 690 showed the presence of other polyhydroxylated alkaloids which appear to
be novel natural products from tentative identification. These seem to be related
biosynthetically to swainsonine.
Some aspects of the biological activity of swainsonine were also investigated
and it was found that it did not inhibit the growth of a range of saprophytic fungi and
bacteria but it was effective against several species of plant-parasitic nematodes both in
vitro and in vivo. It displayed systemic activity after foliar application and persisted in
the tissues of tomato plants for over 5 weeks with no apparent phytotoxicity.